Cancer-fighting protein may help breast tumours resist treatment, Australian study finds

Melbourne, August 14 — Australian researchers have uncovered a surprising reason why breast cancer treatments sometimes stop working, according to a study published in Nature. The research team from Peter MacCallum Cancer Centre discovered that the retinoblastoma (Rb) protein, a protein traditionally thought to act as a barrier against cancer growth, can unexpectedly activate genes tied to estrogen.

Some of these genes can assist cancer cells in resisting treatment and retaining their capacity to proliferate, according to a statement from the cancer center.

Associate Professor Shom Goel, the study's senior author, explained that Rb's role extends beyond merely turning off genes involved in cell division. It can also "activate biological programs that at times work against its own protective effects," Goel stated. The findings provide insight into why CDK4/6 inhibitors, a type of medication, perform best when used in conjunction with endocrine therapy for hormone receptor-positive breast cancer, the most common type of the disease.

Goel elaborated that CDK4/6 inhibitors activate Rb to halt cancer cell division, while endocrine therapy halts estrogen-driven signals that Rb can also trigger. When these approaches work in tandem, they allow the tumor-suppressing capabilities of Rb to take precedence. However, when breast cancers become unresponsive to endocrine therapy, the estrogen-related gene program persists despite treatment, diminishing the effectiveness of CDK4/6 inhibitors, researchers found.

Understanding this unanticipated role of Rb provides a fresh perspective on drug resistance, according to Goel. He emphasized that the discovery could inform the development of new combination therapies to prolong the effectiveness of existing treatments and enhance outcomes for breast cancer patients.